Hereditary and acquired p53 gene mutations in childhood acute lymphoblastic leukemia

The p53 gene was examined in primary lymphoblasts of 25 pediatric patients with acute lymphoblastic leukemia by the RNase protection assay and by single strand conformation polymorphism analysis in 23 of 25 cases. p53 mutations were found to occur, but at a low frequency (4 of 25). While all four mu...

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Bibliographic Details
Published in:The Journal of clinical investigation 1992-02, Vol.89 (2), p.640-647
Main Authors: FELIX, C. A, NAU, M. M, KNUTSEN, T, MINNA, J. D, TAKAHASHI, T, MITSUDOMI, T, CHIBA, I, POPLACK, D. G, REEMAN, G. H, COLE, D. E, LETTERIO, J. J, WHANG-PENG, J
Format: Article
Language:English
Subjects:
Adolescent
Adult
Base Sequence
Biological and medical sciences
Burkitt Lymphoma - genetics
Child
Child, Preschool
Chromosome Deletion
genes
Genes, p53
Hematologic and hematopoietic diseases
Humans
Infant
Infant, Newborn
inheritance
Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis
Li-Fraumeni Syndrome - genetics
Medical sciences
Molecular Sequence Data
Mutation
Polymorphism, Genetic
Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics
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Summary:The p53 gene was examined in primary lymphoblasts of 25 pediatric patients with acute lymphoblastic leukemia by the RNase protection assay and by single strand conformation polymorphism analysis in 23 of 25 cases. p53 mutations were found to occur, but at a low frequency (4 of 25). While all four mutations were identified by single strand conformation polymorphism, the comparative sensitivity of RNase protection was 50% (2 of 4). Heterozygosity was retained at mutated codons in 3 of 4 cases. One pedigree was consistent with the Li-Fraumeni syndrome, and bone marrow from both diagnosis and remission indicated a germline G to T transversion at codon 272 (valine to leucine). Although members of another family were affected with leukemia, a 2-bp deletion in exon 6 was nonhereditary. The other two nonhereditary p53 mutations included a T to G transversion at codon 270 (phenylalanine to cysteine) and a G to C transversion at codon 248 (arginine to proline). These data support the role of both hereditary and acquired p53 mutations in the pathogenesis and/or progression of some cases of childhood acute lymphoblastic leukemia.
ISSN:0021-9738
1558-8238
DOI:10.1172/JCI115630